生物活性

• 描述COX-1 protein, differently from COX-2, is moderately to highly expressed in 99% of high-grade serous tumors, and across all serous tumors compared to endometrioid, mucinous and clear cell tumors. It was demonstrated that the down-regulation of COX-1 gene expression inhibits multiple pro-tumorigenic pathways and that knockdown of COX-1 inhibits pro-tumorigenic functions such as cell viability, clonogenicity, and migration/invasion in COX-1 expressing ovarian cancer cells. Mofezolac is a potent COX-1 inhibitor with an IC₅₀ value of 5.1 nM^[3]. Mofezolac was able to reduce COX-1 expression in LPS (lipopolysaccharide)-activated BV-2 cells accompanied to PGE₂ release reduction and NF-kB activation downregulation. In the in vivo model, both glial fibrillary acidic protein and ionized calcium-binding adapter molecule-1 expression, two markers of inflammation, were reduced by mofezolac to a rank depending on the encephalon area analyzed. The increase of COX-1 expression observed in all the brain sections of LPS-treated mice was selectively downregulated by the in vivo treatment with mofezolac as well as PGE₂ release and Ikβα phosphorylation amount assayed in the brain areas tested^[1].
• 作用机制Leu359, Leu531, Ile523, Tyr355 interact with the mofezolac moiety^[3].